The long range goal of the proposed research is to increase our understanding of the genetic transmission of a variety of medical disorders by undertaking a complete health survey of five related Amish-Mennonite communities. Preliminary evidence from the isolate that has been partially studied suggests that this population has a very high prevalence of certain common disorders (e.g., type II diabetes, heart disease) as well as a high frequency of rare disorders (e.g., Romano-Ward syndrome, nesidioblastosis, situs inversus, Hodgkin's disease). An assessment of the community's kinship structure indicates a high level of inbreeding which is accumulating at a rate sufficient to make it perhaps the most inbred isolate in the U.S. in less than a generation. Since all five isolates are fission products of a single community, they can be expected to share many disorders. The proposed research, accordingly, will fully characterize the genetic structure and health status of these five isolates--a necessary first step to more detailed studies. In addition, the hypothesis that variation at the major histocompatibility complex is maintained by balanced selection (alleged to operate by favoring fetuses who are incompatible with their mothers) will be tested. Because of their extensive coancestry many couples share entire haplotypes identical by descent thereby allowing a powerful direct test of the "heterosis" hypothesis which would be unfeasible in an outbred population. Finally, on a more theoretical level, new approaches to linkage analysis will be derived. It is ironic that the heavy inbreeding which is responsible for the high incidence of rare recessive diseases among Anabaptist sects, is the same factor which renders linkage analysis using traditional maximum likelihood techniques, impractical.